rs5402

Variant names:

• chr3-171009950-T-A
• rs5402
• NM_000340.2:c.496+8A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000340.2(SLC2A2):​c.496+8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,540,942 control chromosomes in the GnomAD database, including 20,411 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5347 hom., cov: 30)
  • Exomes 𝑓: 0.12 (15064 hom.)
• Consequence: SLC2A2 NM_000340.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001880
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.31
• Publications: 13 publications found

Genes affected

SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

SLC2A2 Gene-Disease associations (from GenCC):

• glycogen storage disease due to GLUT2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P
• neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ENSG00000286856 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-171009950-T-A is Benign according to our data. Variant chr3-171009950-T-A is described in ClinVar as Benign. ClinVar VariationId is 130350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.496+8A>T		splice_region_variant, intron_variant	Intron 4 of 10	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.496+8A>T		splice_region_variant, intron_variant	Intron 4 of 10	1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33244 AN: 150672 Hom.: 5330 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00914

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.196

GnomAD2 exomes AF: 0.0892 AC: 16621 AN: 186318 AF XY: 0.0882

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.0740

Gnomad ASJ exome AF: 0.0927

Gnomad EAS exome AF: 0.00250

Gnomad FIN exome AF: 0.0748

Gnomad NFE exome AF: 0.0801

Gnomad OTH exome AF: 0.0912

GnomAD4 exome AF: 0.125 AC: 173204 AN: 1390152 Hom.: 15064 Cov.: 38 AF XY: 0.125 AC XY: 86113 AN XY: 690020

African (AFR) AF: 0.460 AC: 14158 AN: 30798

American (AMR) AF: 0.115 AC: 4592 AN: 39926

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3331 AN: 24948

East Asian (EAS) AF: 0.0141 AC: 545 AN: 38676

South Asian (SAS) AF: 0.143 AC: 11671 AN: 81638

European-Finnish (FIN) AF: 0.120 AC: 5631 AN: 47030

Middle Eastern (MID) AF: 0.152 AC: 824 AN: 5412

European-Non Finnish (NFE) AF: 0.117 AC: 124480 AN: 1064098

Other (OTH) AF: 0.138 AC: 7972 AN: 57626

GnomAD4 genome AF: 0.221 AC: 33292 AN: 150790 Hom.: 5347 Cov.: 30 AF XY: 0.219 AC XY: 16099 AN XY: 73588

African (AFR) AF: 0.456 AC: 18630 AN: 40890

American (AMR) AF: 0.176 AC: 2656 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3464

East Asian (EAS) AF: 0.00917 AC: 47 AN: 5128

South Asian (SAS) AF: 0.149 AC: 706 AN: 4752

European-Finnish (FIN) AF: 0.126 AC: 1322 AN: 10466

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 290

European-Non Finnish (NFE) AF: 0.132 AC: 8924 AN: 67690

Other (OTH) AF: 0.194 AC: 403 AN: 2078

Alfa AF: 0.147 Hom.: 586

Bravo AF: 0.238

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 05, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 10, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Fanconi-Bickel syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.049
DANN	Benign	0.47
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5402; hg19: chr3-170727739;